Abstract
Idiopathic pulmonary fibrosis (IPF), characterized by aggravated alveolar destruction and fibrotic matrix deposition, tendentiously experiences the stage called acute exacerbation IPF (AE-IPF) and progresses to multiple organ damage, especially liver injury. Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury, whereas current animal models induced with bleomycin (BLM) could not completely reflect the pathological manifestations of AE-IPF patients in clinic, and the exact underlying mechanisms are not yet fully explored. In the current study, we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice. This mouse model successfully recapitulated the clinical features of AE-IPF, including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations, as indicated by significant upregulation of Il6, Tnfa, Il1b, Tgfb, fibronectin, and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels. These effects might be attributed to the regulation of Th17 cells. By sharing this novel murine model, we expect to provide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.